Inflammatory responses to lipopolysaccharide are suppressed in 40% energy-restricted mice

To elucidate the suppressive effects of energy restriction on the inflammat ory responses to lipopoly-saccharicle (LPS), mice were divided into a contr ol group (fed 5.0 g diet/d; 71 kJ/d) and a 40% energy-restricted group (fed 3.0 g diet/d; 43 kJ/d) at 8-wk of age. Four weeks later, 25 mug of LPS was intraperitoneally injected. After the LPS injection, interleukin-1 beta, i nterleukin-6 and tumor necrosis factor-a were elevated in serums in the 40% energy-restricted mice and in the controls, but the extent of the elevatio n was significantly lower in the restricted group. The LPS-induced expressi on of inducible nitric oxide synthase in the liver was significantly suppre ssed by the energy restriction. In addition, the LPS-induced elevations of serum aspartate and alanine aminotransferase activities, which are indexes of hepatic injury, were also significantly attenuated in the restricted gro up. Moreover, the extent of LPS-induced alterations in hepatic structure wa s less in the restricted mice than in controls. Serum corticosterone level in the restricted mice was higher than that in the controls before LIPS tre atment (P < 0.05). Furthermore, after LIPS injection, the significantly hig her level of corticosterone was maintained in the restricted mice, although the LPS treatment significantly enhanced the level even in the control gro up. These results suggest that the extreme inflammatory responses to endoto xin are prevented in the 40% energy-restricted mice, and corticosterone par ticipates in the preventive effects.